Since its earliest detection in the northern hemisphere, West Nile (WN) virus has continued to spread rapidly across North America. The first cases were diagnosed in the New York area in 1999, and by 2002 human mortality increased to over 150 cases and the virus spread has continued, reaching as far as California. The appearance of infected/dead birds indicates that there is a large pool of infected mosquitoes in the geographical areas of incidence. To date, there is no effective drug treatment against West Nile virus and methods of surveillance and prevention are not significantly impacting the number of cases of human infection. Thus, the risks of the virus migrating into the southern American continent, as well as an epidemic in underdeveloped countries, are extremely high.
West Nile virus is a member of the flavivirus family. These viruses are small, enveloped, positive-strand RNA viruses that are of concern in many medical and veterinary settings throughout the world. Examples of flaviviruses in addition to West Nile virus include Yellow Fever virus, Japanese Encephalitis virus, and Dengue viruses.
Flavivirus proteins are produced by translation of a single, long open reading frame to generate a polyprotein, which undergoes a complex series of post-translational proteolytic cleavages by a combination of host and viral proteases to generate mature viral proteins (Amberg et al., J. Virol. 73:8083–8094, 1999; Rice, “Flaviviridae,” In Virology, Fields (ed.), Raven-Lippincott, New York, 1995, Volume I, p. 937). The virus structural proteins are arranged in the polyprotein in the order C-prM-E, where “C” is capsid, “prM” (or “pre-membrane”) is a precursor of the viral envelope-bound M (membrane) protein, and “E” is the envelope protein. These proteins are present in the N-terminal region of the polyprotein, while the non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) are located in the C-terminal region of the polyprotein.